Collagen shrinking processes have been used in clinical medicine for various applications. In orthopedics and sports medicine, both laser and radio frequency methods have been utilized for generating the temperature elevation required for collagen phase transition in unstable joint disease and other orthopedic conditions. In otology, lasers have been used to increase the structural integrity of the tympanic membrane in a condition of presbycusis whereby the ear drum becomes somewhat flaccid resulting in hearing impairment in the vocal range.
Thermal keratoplasty, another collagen shrinkage modality, is now an accepted refractive surgical process for altering the front surface radius of the cornea in the treatment of hyperopia. Both radio frequency and coherent energy are utilized in the thermal phase transition, which results in the stromal collagen shrinkage.
A novel process, which remedies the loss of amplitude and range of focus in presbyopia, has been disclosed in previous filings. A collateral benefit of this process applies to the treatment of glaucoma and ocular hypertension. This process also utilizes collagen shrinkage targeting the collagenous ciliary muscle tendon and sclera.
In each application of collagen shrinkage to derive a beneficial effect, permanence of effect has been elusive due to wound repair processes incited as an adjunctive event in each application. Loss of effect as a function of time, otherwise known as regression of the desired effect, has been shown to result from the wound repair process. Regression has, therefore, been a significant problem, which has frustrated attempts to design procedures that are both efficacious and predictable, while remaining safe.
It then would seem to be advantageous to be able to control, ameliorate, and/or obtund this wound repair cascade during and following these various collagen shrinkage processes. The management of these repair events would predispose to long term and, possibly, permanent beneficial results resulting from the collagen phase transition.
All attempts to alter the refractive surfaces of the cornea are, by their very nature, an alteration of the integrity of the corneal tissue. Each method of corneal recurvature requires some mode of traumatic intervention, although some methods are more invasive than others. As one creates ever more complex radius modification upon the anterior surface or within the corneal stroma, the trauma is compounded. In view of this trauma, the efficacy and predictability of each method becomes an important issue.
Interactive wave front-guided refractive modification has been integrated into the process in an attempt to diminish the aberrations generated by the various refractive surface in the image path. While this modality has the advantage of improving the visual result of refractive intervention, this process does nothing to ameliorate the wound repair cascade. Refractive regression will still be related to the change in tissue structural bio-mechanics induced by the trauma.
Observations of the post-operative corneal radius creep and deformation have elicited an understanding of the changes that affect the stability and predictability of the desired effect. Some of the changes seen in regression are indeed, paradoxical, while others appear to be directly related to the type of trauma sustained. The molecular and cellular biological responses manifested by these processes are the result of several separate, but integrated events. These events include, but are not limited to cellular apoptosis, cellular necrosis, accumulation of stress or heat shock proteins, and destruction of the lamellar-stabilizing molecular cross-links.
Current treatments, which reduce the fibrosis and scarring that accompanies wound repair, include antimetabolites, immunosuppressants, corticosteroids, and various cytokines or growth factors such as TGF-β. These methods have been used to reduce or prevent corneal haze in refractive surgery. Mitomycin C, an anti-cancer drug, has been used for this purpose, but this drug does not address the complex issues associated with the wound repair cascade. Mitomycin C is a toxic drug, which can cause serious collateral complications and caution must be observed in its use.
Refractive keratoplasty is defined as any interventional process by which the corneal front radius of curvature is altered to improve visual refractive function.
A need clearly exists to find a way to prevent the regression that characterizes so many collagen shrinkage processes with special reference to thermally mediated processes addressing the treatment of presbyopia and the collateral treatment of chronic open angle glaucoma.
In one aspect, this invention discloses methods and devices for preventing the wound repair cascade, and subsequent loss of effect, in the treatment of presbyopia, in the treatment of the loss of the range and amplitude of accommodation, in the treatment of chronic open angle glaucoma, and in the treatment of ocular hypertension by collagen shrinkage modalities.